Invariant natural killer T cells (NKT) are a subset of T cells that are implicated in a broad range of diseases. In some circumstances they can enhance the response to infection (Kinjo, Illarionov et al. 2011) and cancer (Wu, Lin et al. 2011) but also possess the ability to suppress autoimmune disease (Hong, Wilson et al. 2001) and allergic disease (Knothe, Mutschler et al. 2011). Activation of NKT cells can also lead to undesirable immune responses as related to allergy (Wingender, Rogers et al. 2011), autoimmunity (Zeng, Liu et al. 2003) and atherosclerosis (Tupin, Nicoletti et al. 2004).
Unlike conventional T cells that are restricted by major histocompatibility complex (MHC) molecules that present peptide antigens, NKT cells are uniquely restricted by CD1d proteins (Bendelac, Savage et al. 2007). CD1d proteins belong to the CD1 family that contains five members, CD1a-e. Like MHC molecules, the CD1 family members all contain an antigen binding region that is flanked by two anti-parallel α-helices that sit above a β-sheet. Unlike MHC molecules, the binding region of the CD1 proteins contain two large hydrophobic binding pockets that are suited to bind lipid antigens rather than peptide-based antigens (Li, Girardi et al. 2010). α-Galactosylceramide (α-GalCer) is the most studied NKT cell antigen and potently activates human and mouse NKT cells (Kawano, Cui et al. 1997). In animal studies, α-GalCer is reported to be useful in the treatment of a number of diseases including cancer (Morita, Motoki et al. 1995; Motoki, Morita et al. 1995) and autoimmune disease (Hong, Wilson et al. 2001). The compound has also been shown to function as a potent vaccine adjuvant in the treatment and prophylaxis of cancer (Silk, Hermans et al. 2004), infectious disease (Li, Fujio et al. 2010) and allergy (Knothe, Mutschler et al. 2011). This adjuvant activity has been attributed to stimulatory interactions between activated NKT cells and dendritic cells (DCs), the most potent antigen-presenting cells in the body. As a consequence, the DCs are rendered capable of promoting strong adaptive immune responses (Fujii, Shimizu et al. 2003; Hermans, Silk et al. 2003).
There is considerable interest in therapeutic vaccines for the treatment of cancer. The aim is to stimulate clonal expansion of T cells within a host that are capable of recognising and killing tumour cells, leaving normal tissues intact. This specificity relies on recognition of unique, tumour-derived, protein fragments presented by MHC molecules on the tumour cell surface. Vaccines used in this context typically involve injection of the defined tumour-associated “tumour antigens”, or their peptide fragments, together with immune adjuvants capable of driving an immune response. In the absence of such adjuvants, the opposite outcome may ensue, with the tumour antigens actually being “tolerated” by the immune system rather than provoking tumour rejection. Advances in this therapy are therefore dependent on appropriate combinations of antigen and adjuvant (Speiser and Romero 2010) and how these combinations are presented to the immune system (Black, Trent et al. 2010).
When incorporated into a vaccine, α-GalCer must first be acquired by antigen-presenting cells in the host, and then presented to NKT cells within the local environment (Fujii, Shimizu et al. 2003; Hermans, Silk et al. 2003). This process brings the two cell types into close association, permitting stimulatory signals to be passed from NKT cell to antigen-presenting cell.

Although α-GalCer has considerable biological activity it does have limitations such as poor solubility (Ebensen, Link et al. 2007), lack of efficacy in human clinical trials (Giaccone, Punt et al. 2002), promotion of T cell anergy (Parekh, Wilson et al. 2005) and the generation of both Th1 and Th2 cytokines that may contribute to mixed results in model studies.
It is an object of the invention to provide novel compounds or vaccines useful as agents for treating diseases or conditions relating to cancer, infection, autoimmune disease, atopic disorders or cancer, or to at least provide a useful alternative.
Any reference or discussion in relation to prior art publications within this specification does not constitute an admission that such references form part of the common general knowledge in the art in any country or jurisdiction.
Throughout the description and the claims, the words “comprise”, “comprising” and the like, are intended to mean in an inclusive sense and not an exclusive or exhaustive sense, that is to say, “including, but not limited to”.